Vitamin C supplementation attenuates oxidative stress and improves erythrocyte deformability in cardiac surgery with cardiopulmonary bypass.

Cardiopulmonary bypass (CPB) depletes endogenous Vitamin C and generates oxidative stress in cardiac surgery. This study aimed to clarify whether Vitamin C supplementation reduces oxidant production and improves erythrocyte deformability in cardiac surgery with CPB. In a randomized and controlled design, 30 eligible patients undergoing cardiac surgery with hypothermic CPB were equally assigned to the Vitamin C group and control group. Subjects of the Vitamin C group and control group received an intravenous infusion of Vitamin C 20 mg·kg-1 and a placebo during rewarming period of CPB, respectively. We measured the plasma level of reactive oxygen species (ROS) and phosphorylation levels of non-muscle myosin IIA (NMIIA) in erythrocyte membrane, as an index of erythrocyte deformability, before and after CPB. Vitamin C supplementation attenuated the surge in plasma ROS after CPB, mean 1.661 ± standard deviation 0.801 folds in the Vitamin C group and 2.743 ± 1.802 in the control group. The tyrosine phosphorylation level of NMIIA after CPB was upregulated in the Vitamin C group compared to the control group, 2.159 ± 0.887 folds and 1.384 ± 0.445 (P = 0.0237). In addition, the phosphorylation of vasodilator-stimulated phosphoprotein (VASP) and focal adhesion kinase (FAK) in erythrocytes was concurrently enhanced in the Vitamin C group after CPB. The phosphorylation level of endothelial nitric oxide synthase in erythrocytes was significantly increased in the Vitamin C group (1.734 ± 0.371 folds) compared to control group (1.102 ± 0.249; P = 0.0061). Patients receiving Vitamin C had lower intraoperative blood loss and higher systemic vascular resistance after CPB compared to controls. Vitamin C supplementation attenuates oxidative stress and improves erythrocyte deformability via VASP/FAK signaling pathway in erythrocytes during CPB.

High-dose nitroglycerin administered during rewarming preserves erythrocyte deformability in cardiac surgery with cardiopulmonary bypass.

OBJECTIVE: We aimed to determine whether high-dose nitroglycerin, a nitric oxide donor, preserves erythrocyte deformability during cardiopulmonary bypass and examines the signaling pathway of nitric oxide in erythrocytes. METHODS: In a randomized and controlled fashion, forty-two patients undergoing cardiac surgery with hypothermic cardiopulmonary bypass were allocated to high-dose (N = 21) and low-dose groups (N = 21). During rewarming period, patients were given intravenous nitroglycerin with an infusion rate 5 and 1 µg·kg-1 ·min-1 in high-dose and low-dose groups, respectively. Tyrosine phosphorylation level of non-muscle myosin IIA in erythrocyte membrane was used as an index of erythrocyte deformability and analyzed using immunoblotting. RESULTS: Tyrosine phosphorylation of non-muscle myosin IIA was significantly enhanced after bypass in high-dose group (3.729 ± 1.700 folds, P = .011) but not low-dose group (1.545 ± 0.595 folds, P = .076). Phosphorylation of aquaporin 1, vasodilator-stimulated phosphoprotein, and focal adhesion kinase in erythrocyte membrane was also upregulated in high-dose group after bypass. Besides, plasma nitric oxide level was highly correlated with fold change of non-muscle myosin IIA phosphorylation (Pearson's correlation coefficient .871). CONCLUSIONS: High-dose nitroglycerin administered during cardiopulmonary bypass improves erythrocyte deformability through activating phosphorylation of aquaporin 1, vasodilator-stimulated phosphoprotein, and focal adhesion kinase in erythrocytes.

Stage-dependent angiopoietin-Tie2 and nitric oxide signaling of erythrocytes in response to surgical trauma in head and neck cancer.

BACKGROUND: Angiopoietin-Tie2 and nitric oxide pathway is crucial in tumor angiogenesis and closely correlates with tumor development, growth, and metastasis. This study aimed to investigate the angiopoietin-Tie2 and nitric oxide signaling of the erythrocyte membrane in response to surgical trauma in head and neck cancer. METHODS: We prospectively enrolled the patients with histology-proven head and neck squamous cell carcinoma undergoing surgical resection of primary tumors at the medical center between August and November 2019. We measured the preoperative and postoperative levels of angiopoietin-1, angiopoietin-2 in plasma using enzyme-linked immunosorbent assays, nitric oxide in plasma using nitrate/nitrite colorimetric assays, and Tie2 phosphorylation in erythrocyte membrane using Western blotting. RESULTS: The plasma angiopoietin-1 was downregulated from the median 971.3 pg/mL (interquartile range [IQR] 532.1-1569.3) to 417.9 (IQR 270.5-597.3) after tumor resection (p = 0.0020). Conversely, the plasma angiopoietin-2 was enhanced from 1173.6 pg/mL (IQR 977.7-1450.2) to 2353.7 (IQR 1352.4-2954.3) after surgery (p = 0.0021), with a concomitant increase in plasma nitric oxide level from 7.73 µM (IQR 5.39-10.06) to 10.50 (IQR 7.65-14.18) after surgical resection (p = 0.0093). Subgroup analyses further showed the angiopoietin-Tie2 and nitric oxide signaling was significant only in stage III and IV cancer. CONCLUSIONS: The dynamic change of angiopoietin-Tie2 signaling in the erythrocyte membrane along with the enhanced nitric oxide in plasma after tumor resection suggests erythrocytes play a significant role in modulating surgery-induced angiogenesis, which may provide a novel marker for cancer surveillance and control.

Glucose reduces the osmopressor response in connection with the tyrosine phosphorylation of focal adhesion kinase in red blood cells.

Glucose ingestion attenuates the water ingestion-induced increase in the total peripheral vascular resistance and orthostatic tolerance. We investigated the gastrointestinal physiology of glucose by examining the effect of glucose ingestion on the functional expression of focal adhesion kinase (FAK) in red blood cell (RBC) membrane. This study was performed in 24 young, healthy subjects. Blood samples were collected at 5 min before and 25 min and 50 min after an ingestion of 10% glucose water 500 mL, water 500 mL, or normal saline 500 mL. We determined glucose and osmolality in plasma, and phosphorylation of aquaporin 1 (AQP1), glucose transporter 1 (Glut1), and FAK in RBC membrane. Our results showed that glucose ingestion reduced the rise of peripheral vascular resistance after water ingestion and upregulated the serine phosphorylation of Glut1. It also lowered both the serine phosphorylation of FAK and tyrosine phosphorylation of AQP1, compared with the ingestion of either water or saline. In an ex vivo experiment, glucose activated the Glut1 receptor and subsequently reduced the expression of FAK compared with 0.8% saline alone. We concluded that glucose activates Glut1 and subsequently lowers the functional expression of FAK, a cytoskeleton protein of RBCs. The functional change in the RBC membrane proteins in connection with the attenuation of osmopressor response may elucidate the pathophysiology of glucose in postprandial hypotension.

Intravenous loading of nitroglycerin during rewarming of cardiopulmonary bypass improves metabolic homeostasis in cardiac surgery: a retrospective analysis.

PURPOSE: The aim of the study was to evaluate the effects of high-dose nitroglycerine (NTG) on glucose metabolism, tissue oxygenation and postoperative recovery in cardiac surgical patients. METHODS: Cardiac surgical patients in the retrospective survey were classified into two groups based on the NTG regimen. NTG group had intravenous loading of NTG (infusion rate 10-20 mg/h with total dose of ≥0.5 mg/kg) starting at rewarming of cardiopulmonary bypass (CPB) (n = 101), and control group had no intravenous loading of NTG (n = 151). Data for intraoperative plasma glucose and lactate levels, and regular insulin consumption were collected. Propensity score methodology was utilized to adjust for potential confounders. RESULTS: After adjustment for propensity score, the plasma glucose was significantly lower in the NTG group during (161 ± 39 versus 179 ± 45 mg/dl, p = 0.005) and after CPB (167 ± 41 versus 184 ± 48 mg/dl, p = 0.012). Total consumption of regular insulin was significantly lower in the NTG group, median 8 (range 0-50) versus 13 (0-90) international units, p = 0.005. There was a trend towards statistical significance in a lower incidence of hyperlactatemia (>2.2 mmol/l) in the NTG group during CPB, 21/100 (21 %) versus 40/132 (30.3 %), p = 0.065. The mixed venous oxygen saturation in the intensive care unit was higher in the NTG group, 65 ± 9 versus 62 ± 11 %, p = 0.056. CONCLUSIONS: Intravenous loading of NTG during and after CPB is safe and effective for attenuating the hyperglycemic response and reduce the incidence of hyperlactatemia during cardiac surgery with CPB.

Dose proportionality and pharmacokinetics of extended-release (OROS®) hydromorphone: a phase 1, open-label, randomized, crossover study in healthy Taiwanese subjects.

OBJECTIVES: Osmotic-controlled release oral delivery system (OROS®) hydromorphone - an extended-release preparation - is recommended long-term therapy for chronic pain patients. Dose proportionality of OROS hydromorphone has been shown in healthy Caucasian volunteers; however, no studies have been conducted in Asian populations. To determine whether ethnic differences affect the drug's pharmacokinetic (PK) profile, we evaluated the dose proportionality of OROS hydromorphone in healthy Taiwanese adults. METHODS: This 12-week, open-label, 4-way crossover, phase 1 study randomly assigned subjects to 1 of 4 treatment sequences - single oral dose OROS hydromorphone: 8 mg, 16 mg, 32 mg, or 64 mg - along with 50 mg naltrexone. Dose proportionality was assessed using a linear mixed-effects model to estimate the slope of the regression line and its 90% CI for Cmax, AUC0-48h, and AUClast. Descriptive statistics measured plasma hydromorphone concentrations, PK parameters, laboratory analytes, and vital signs. RESULTS: 23 subjects completed the study; a single-dose of OROS hydromorphone increased plasma concentration steadily for 6 hours and sustained it at or near maximum levels for ~ 24 hours. After dose normalization to a 16 mg dose, all studied doses demonstrated dose proportionality for Cmax, AUClast, and AUC0-48h,as the slopes of the regression lines for Cmax, AUClast, and AUC0-48h were close to zero, and the 90% CIs within pre-specified limits. Adverse events were as expected for hydromorphone administered with concomitant naltrexone. CONCLUSIONS: Single doses of 8 mg, 16 mg, 32 mg, and 64 mg of OROS hydromorphone were found to be dose proportional for Cmax, AUClast, and AUC0-48h and were generally safe and well-tolerated in healthy Taiwanese adults.

Pharmacokinetics of sevoflurane elimination from respiratory gas and blood after coronary artery bypass grafting surgery.

PURPOSE: Sevoflurane, with a relative low blood-gas partition coefficient, is an ideal anesthetic to achieve rapid offset and recovery from general anesthesia. This study will determine the profiles of four concentration-time curves to characterize the pharmacokinetics of sevoflurane elimination. METHODS: Eight patients (aged 54-76 years) undergoing coronary arterial bypass grafting surgery were enrolled in this study. At the end of surgery, anesthetic gas and blood were sampled 20 min before and after stopping sevoflurane administration, with prior maintenance of a fixed 5% inspired sevoflurane (CIsev) in 6 L/min oxygen flow for 60 min before the cessation of sevoflurane administration for the subsequent 20 min elimination. An infrared analyzer was used to determine both CIsev and end-tidal sevoflurane (CEsev). The sevoflurane concentrations in the internal jugular-bulb (Jsev), arterial (Asev) and pulmonary arterial blood (PAsev) were analyzed by gas chromatography, and cardiac output was measured using an Opti-Q pulmonary artery catheter. RESULTS: A bi-exponential decay function was the best fit for the CEsev,Jsev, Asev, and PAsev time curves. There were two distinct components, the initial 5-min fast or distribution phase and the subsequent 15-min slow or elimination phase. Before cessation of the sevoflurane supplement, the step-down concentration of sevoflurane was listed in the following order: CIsev > CEsev > Asev ≧ Jsev > PAsev. During the elimination phase, the fastest decay occurred in CEsev, followed by Jsev, Asev and PAsev. Therefore, a reverse step-down pattern was observed (PAsev > Asev ≧ Jsev > CEsev) after 20 min. The ratio of Asev to CEsev was 89% at baseline before stopping sevoflurane administration, but the ratio of Asev to CEsev increased to 128% at the twentieth min of the sevoflurane elimination phase. CONCLUSIONS: During elimination, the initial washout of sevoflurane from the functional residual capacity of the lungs was reflected in the fast component of the CEsev, Jsev, Asev, and PAsev time curves. In contrast, the slow component was dominated by the tangible effects of the physiological membrane barriers, such as the alveoli-pulmonary capillary and blood-brain barriers.

Pharmacokinetics of desflurane uptake and disposition in piglets.

Introduction: Many respiratory but few arterial blood pharmacokinetics of desflurane uptake and disposition have been investigated. We explored the pharmacokinetic parameters in piglets by comparing inspiratory, end-tidal, arterial blood, and mixed venous blood concentrations of desflurane. Methods: Seven piglets were administered inspiratory 6% desflurane by inhalation over 2 h, followed by a 2-h disposition phase. Inspiratory and end-tidal concentrations were detected using an infrared analyzer. Femoral arterial blood and pulmonary artery mixed venous blood were sampled to determine desflurane concentrations by gas chromatography at 1, 3, 5, 10, 20, 30, 40, 50, 60, 80, 100, and 120 min during each uptake and disposition phase. Respiratory and hemodynamic parameters were measured simultaneously. Body uptake and disposition rates were calculated by multiplying the difference between the arterial and pulmonary artery blood concentrations by the cardiac output. Results: The rates of desflurane body uptake increased considerably in the initial 5 min (79.8 ml.min-1) and then declined slowly until 120 min (27.0 ml.min-1). Similar characteristics of washout were noted during the subsequent disposition phase. Concentration-time curves of end-tidal, arterial, and pulmonary artery blood concentrations fitted well to zero-order input and first-order disposition kinetics. Arterial and pulmonary artery blood concentrations were best fitted using a two-compartment model. After 2 h, only 21.9% of the desflurane administered had been eliminated from the body. Conclusion: Under a fixed inspiratory concentration, desflurane body uptake in piglets corresponded to constant zero-order infusion, and the 2-h disposition pattern followed first-order kinetics and best fitted to a two-compartment model.

Salivary alpha-amylase as a biomarker for the osmopressor response in healthy adults.

Water ingestion induces a sympathetically mediated increase in blood pressure in dysautonomic patients and the elderly, but not consistently in young healthy subjects. The aim of study was to determine the extent of the pressor response and changes of sympathetic activity biomarker salivary alpha-amylase (sAA) after water ingestion in young healthy subjects. Compared with ingestion of 50 mL of water, the blood pressure, total peripheral resistance and sAA significantly increased and the plasma osmolality decreased 25 min after drinking 500 mL of water. The results confirm the osmopressor response in young subjects and suggest that sAA may be used as a non-invasive marker of sympathetic activity in future studies.

Simultaneous determination of nalbuphine and its prodrug sebacoly dinalbuphine ester in human plasma by ultra-performance liquid chromatography-tandem mass spectrometry and its application to pharmacokinetic study in humans.

A rapid, simple, sensitive and selective ultraperformance liquid chromatography-tandem spectrometry (UPLC-MS/MS) method for the determination of nalbuphine and its prodrug sebacoly dinalbuphine ester (SDE) was developed and validated in human plasma. The sample pretreatment involves basification and iterative liquid-liquid extraction with ethyl-ether-dichloromethane (7:3, v/v) solution, followed by LC separation and positive electrospray ionization (ESI) API-3000 mass spectrometry detection. The chromatography was on a Waters Acquity UPLC BEH HILIC column (2.1 × 100 mm, 1.7 µm). The mobile phase was composed of acetonitrile and water (83:17, v/v) that contained 0.2% formic acid and 4 mm ammonium formate at a flow rate of 0.25 mL/min. Ethylmorphine and naloxine were selected as the SDE and nalbuphine internal standard (IS), respectively. The calibration curve for both was linear over the range from 0.05 to 20 ng/mL, with correlation coefficients ≥0.995. The lower limit of quantification was set at 0.05 ng/mL. The intra- and inter-day precision values for nalbuphine and SDE were acceptable as per FDA guidelines. The method was applied successfully to determine nalbuphine concentration in human plasma samples obtained from four Taiwanese volunteers receiving intramuscularly administration of sebacoyl dinalbuphine ester. The method is sensitive, selective and directly applicable to human pharmacokinetic studies involving nalbuphine.

Pharmacokinetics of desflurane elimination from respiratory gas and blood during the 20 minutes after cardiac surgery.

BACKGROUND/PURPOSE: Desflurane, with a low blood-gas partition coefficient, is an ideal anesthetic to achieve rapid offset and recovery from general anesthesia. Investigation of desflurane elimination from blood and respiratory gas should provide useful information with respect to a patient's recovery from anesthesia. Therefore, this study is designed to characterize the pharmacokinetics of desflurane elimination after cardiac surgery. METHODS: Sixteen patients undergoing coronary artery bypass graft surgery were enrolled. At the end of surgery, multiple gas and blood samples were taken in the 20 minutes before and after stopping desflurane administration, with prior maintenance of a fixed 7% inspired desflurane in 6 L/minute oxygen flow for 60 minutes before the cessation. The blood desflurane concentrations, including internal jugular-bulb blood (Jdes), arterial blood (Ades) and pulmonary arterial blood (PAdes) were analyzed using gas chromatography. The inspiratory desflurane concentration (CIdes) and end-tidal desflurane (CEdes) were measured with an infrared analyzer, and cardiac output was measured using an Opti-Q pulmonary artery catheter. RESULTS: Before cessation of desflurane administration, the inspiratory desflurane concentration (CIdes) was relatively higher than end-tidal (CEdes), arterial (Ades), internal jugular-bulb blood (Jdes), and pulmonary (PAdes) concentrations in sequence (CIdes > CEdes > Ades≈ Jdes > PAdes). During the elimination phase, rapid decay occurred in CEdes, followed by Jdes, Ades and PAdes. Twenty minutes after stopping desflurane administration, the desflurane concentrations were: PAdes > Ades≈ Jdes > CEdes. The decay curves of desflurane concentrations demonstrated two distinct elimination components: an initial, fast 5-minute component followed by a slow 15-minute component. CONCLUSION: Desflurane is eliminated fastest from the lungs, as indicated by CEdes, compared to elimination from circulating blood. The initial, rapid 5-minute desflurane washout reflected the diluting effect of functional residual capacity of the lungs.

Hyperventilation accelerates rise in arterial blood concentrations of sevoflurane in gynecologic patients.

PURPOSE: We investigated whether ventilation volumes affected arterial blood sevoflurane concentration (A (sev)) and its uptake into the body during general anesthesia. METHODS: Thirty female patients undergoing elective gynecologic surgery were randomly allocated into three groups: hyperventilation, normal ventilation, and hypoventilation. Inspiratory (CI(sev)) and end-tidal ((sev)) sevoflurane concentrations were routinely measured by infrared analysis, and A (sev) were analyzed by gas chromatography for 40 min after intubation. Cardiac index and total peripheral vascular resistance were measured with a Finometer. RESULTS: During the first 10 min after sevoflurane administration, A (sev) in the hyperventilation group was the highest and differed significantly from those in the normal ventilation group, followed by those in the hypoventilation group. In addition, hyperventilation significantly increased the slope of A (sev) over time in the first 5 min, but there were no differences in slopes in the 5-10, 10-20, and 20-40 min periods, which indicates no difference in sevoflurane bodily uptake among the three groups after 5 min. CONCLUSION: Hyperventilation accelerated the rate of A (sev) increase immediately after sevoflurane administration, which was time dependent with respect to different alveolar ventilation levels.

Water ingestion reduces skin blood flow through sympathetic vasoconstriction.

OBJECTIVE: Water ingestion induces a pressor effect in patients with efferent baroreflex impairment and a mild pressor effect in elderly healthy subjects. However, water raised the total peripheral vascular resistance (TPR) without a prominent change in blood pressure in young healthy subjects. We try to investigate whether water elicits a cardiovascular response via regulating regional skin blood flow (SkBF) in young healthy subjects. METHODS: In a randomized, controlled, crossover fashion, 15 healthy male subjects (19-27 years old) ingested either 500 (water session) or 50 ml of water (control). The heart rate, blood pressure, cardiac index, and TPR were measured using a Task Force Monitor. A laser Doppler velocimeter was used to determine the change in the SkBF at the left thenar eminence. Plasma catecholamines and their metabolites were also measured. RESULTS: At 25 min after ingestion of 500 ml water, the cardiac index and SkBF significantly decreased compared to control. In contrast, the TPR significantly increased after ingestion of 500 ml water. Plasma dihydroxyphenylalanine significantly increased at 25 min after water. INTERPRETATION: Water ingestion decreases the cardiac index to compensate for the increase in the TPR, leading to no net change in blood pressure in young healthy subjects. This study suggests that water decreases the SkBF, a mechanism that might account partly for the nature of osmopressor response to water in young healthy subjects.

Discrepant End-Tidal Concentrations of Sevoflurane at the Same A-Line Autoregressive Index Level during Induction of General Anesthesia: An Observational Study.

BACKGROUND: The A-Line Autoregressive Index (AAI), which is derived from auditory evoked potentials, has been used for determining anesthetic depth. This study verified the correlation between AAI values and the corresponding end-tidal concentrations of sevoflurane during general anesthesia induction. METHODS: Thirty young male adults undergoing elective minor orthopedic surgery were sequentially allocated to receive inspiratory 3%, 5%, or 6% sevoflurane for mask induction, followed by mechanical ventilation after tracheal intubation. The inspiratory, end-tidal and estimated jugular bulb concentrations of sevoflurane were recorded at three target AAI values: below 20, below 10, and at the start of burst suppression. RESULTS: The mean time to loss of consciousness in the 6% sevoflurane group was shorter than that in the 5% and 3% groups; however, the groups had comparable AAI values (range: 16-45). The 6% group had a higher end-tidal concentration (4.5% ± 0.2% vs. 3.8% ± 0.2%, p < 0.05) than did the 5% group, despite having the same target anesthetic levels by AAI score ≤10, whereas the estimated jugular bulb concentrations were comparable (1.9% vs. 1.9%) in both groups. CONCLUSIONS: Following mechanical ventilation with inspiratory 3%, 5%, or 6% sevoflurane, the end-tidal concentrations were discrepant at the same end points of AAI levels, despite similar estimated jugular bulb concentrations of sevoflurane. Thus, conventional alveolar concentration may overestimate anesthesia depth during rapid wash-in of sevoflurane.

Chronic opioid therapy in patients with chronic noncancer pain in Taiwan.

PURPOSE: Our aim was to analyze the physiopsychosocial variables in patients with long-term opioid therapy for chronic noncancer pain (CNCP) in Taiwan. METHODS: Patients registered in the database of the National Bureau of Controlled Drugs (NBCD), Taiwan, were interviewed and completed questionnaires on pain assessment and interference in quality of life, using the Taiwanese version of the Brief Pain Inventory, and questionnaires on depressive status, using the Chinese version of the Beck Depression Inventory-II; in addition, they completed questionnaires on the adverse effects of the opioid therapy and the use of complementary and alternative medicine. RESULTS: Of 114 patients registered at the NBCD, Taiwan, in August 2001, 61 completed the interviewing procedures and questionnaires. The durations of pain and opioid administration were 93.6 ± 84.3 months (range, 10-480, median 72) and 54.2 ± 57.6 months (range, 6-240, median 30), respectively. Significantly reduced pain intensity (range, 8.8 ± 2.0 to 3.2 ± 2.5) and pain-induced interference with general activity (8.2 ± 2.6 to 3.5 ± 2.5), in addition to improvements in mood, walking ability, normal work, relationships with other people, sleep, and enjoyment of life, indicated remarkably improved quality of life after chronic opioid therapy. The major adverse effects of the opioids were constipation (48%), dry mouth (30%), and nausea and vomiting (21%). Almost half of the patients reported decreases in sexual desire and capability. Up to 60% of the patients received alternative medicine, including acupuncture and herbal drugs. Despite the improved quality of life, 31 of the 61 patients stated that they had moderate or severe depression. CONCLUSIONS: The long-term use of opioids provided significant improvement of pain relief and quality of life in these patients with CNCP; this therapy is a good solution if other modalities are not effective or useful.

Effects of changes in alveolar ventilation on isoflurane arterial blood concentration and its uptake into the human body.

We investigated whether minute alveolar ventilation affects isoflurane concentration in arterial blood and uptake of isoflurane into the body. Thirty female patients scheduled to undergo elective gynecological surgery were randomly assigned to one of three groups: i.e. hyperventilation, normal ventilation and hypoventilation. Inspiratory (CIiso) and end-tidal (CEiso) concentrations of isoflurane were measured by infrared analysis, and arterial blood isoflurane concentration (Aiso) was analyzed by gas chromatography. Cardiac index was measured by Doppler ultrasonography. The body uptake of isoflurane was determined by multiplying alveolar ventilation by the gradient of CIiso-CEiso. Aiso was highest in the hyperventilation group (significant), followed by the normal ventilation and hypoventilation groups, during the 40-min study. During the first 10 min of the study, the slope of the Aiso-over-time curve was highest in the hyperventilation group, followed by the normal ventilation group and the hypoventilation group. During the second half of the study (20-40 min), the slope Aiso-over-time curve did not differ among the three groups. Changes in ventilation affected the concentration of isoflurane in arterial blood but did not significantly alter the uptake of it during the last 20 min of the study. The change of alveolar ventilation altered the speed of functional residual capacity wash-in by isoflurane, which was the integral factor influencing Aiso and body uptake of isoflurane.

The effect of high-dose nitroglycerin on the cerebral saturation and renal function in cardiac surgery: A propensity score analysis.

BACKGROUND: The aim of the study was to evaluate the effects of high-dose nitroglycerine administered during cardiopulmonary bypass on the intraoperative cerebral saturation and postoperative serum creatinine concentration in cardiac surgery. METHODS: In a retrospective cohort study, a total of 239 patients undergoing cardiac surgery with cardiopulmonary bypass at a tertiary medical center were included. General anesthesia consisted of volatile anesthetic and either intravenous loading of high-dose nitroglycerin (infusion rate 10 to 20 mg·h with a total dose of ≥0.5 mg·kg) starting from rewarming of cardiopulmonary bypass throughout the end of the surgery (NTG group; N = 96) or without high-dose nitroglycerin (control group; N = 143). Data for intraoperative cerebral saturation and serum creatinine concentrations before and after cardiac surgery were collected. Propensity score method was used to adjust for potential confounders. RESULTS: Patients receiving high-dose nitroglycerin had significantly lower mean arterial pressure and hematocrit levels during and after cardiopulmonary bypass. The risk of intraoperative cerebral desaturation was left-sided 23.9% versus 38.5% (p = 0.023), right-sided 28.1% versus 35.7% in the NTG and control groups, respectively. The risk of new-onset stroke and postoperative dialysis was 2.1% versus 6.3% and 1.0% versus 3.5% in the NTG and control groups, respectively. CONCLUSION: An infusion of high-dose nitroglycerin initiating at rewarming of cardiopulmonary bypass and throughout the postbypass interval may induce hypotension and hemodilution in cardiac surgical patients. Cerebral saturation and renal function were well maintained without increasing the risk of stroke and renal replacement therapy after cardiac surgery with cardiopulmonary bypass.

Pharmacokinetics of isoflurane in human blood.

Investigation of isoflurane washout from the human body and brain provides more precise information about elimination in anesthesia. The elimination pattern of isoflurane remains poorly quantified, and therefore this study tried to clarify the pharmacokinetic pattern of isoflurane elimination. Sixteen patients (aged 48-78 years), undergoing coronary arterial bypass grafting surgery were enrolled in this study. Sixty minutes prior to the end of surgery, we kept a fixed 2% inspired isoflurane in 6,000 ml min(-1) oxygen flow. Isoflurane supplement was then discontinued to study the 20-min isoflurane elimination. An infrared analyzer was used to determine both inspired isoflurane and end-tidal isoflurane. The isoflurane concentration in the internal jugular bulb blood, arterial blood and pulmonary arterial blood were analyzed by gas chromatography. Biexponential decay function was the best fitted for the end-tidal isoflurane- and arterial blood isoflurane-time curves. There were two distinct components, including initial 5-min fast component and the next 15-min slow component. Monoexponential decay function was the best fitted for the pulmonary arterial blood- and jugular bulb blood-time curves. During elimination, the initial washout of isoflurane from functional residual capacity of lungs is reflected in the fast component of the isoflurane concentration time curves. The later slow component is dominated by the tangible manifestation of physiological membrane barriers, including the existence of alveoli-pulmonary capillary, blood-brain barriers.

Arterial blood concentration of sevoflurane during single-breath induction and tracheal intubation in gynecologic patients.

STUDY OBJECTIVE: To investigate sevoflurane blood concentrations on loss of consciousness during single-breath induction and ensuing tidal volume ventilation. DESIGN: Prospective study. SETTING: Operating room, medical center. PATIENTS: 12 ASA physical status I and II women scheduled for for gynecologic surgery with general anesthesia. INTERVENTIONS: All patients were instructed in the vital capacity technique for inhalation induction with primed inspired sevoflurane greater than 7% in 6 L per minute oxygen. Immediately after loss of consciousness, assisted tidal volume ventilation with a fixed 3.5% of sevoflurane was applied for 9 minutes. Tracheal intubation was performed for each patient following succinylcholine 1.5 mg/kg. MEASUREMENTS: Inspired and end-expired sevoflurane concentration, blood pressure, and heart rate were recorded. Meanwhile, arterial blood samples were collected via a radial arterial catheter on loss of consciousness as the 0 minute and at the following 1.5th, 3rd, 4.5th, 6th, and 9th minute and determined for sevoflurane concentrations by gas chromatography. MAIN RESULTS: All 12 patients achieved vital capacity induction uneventfully. The mean time of loss of consciousness was 63.0 +/- 16.6 seconds. The arterial blood concentration of sevoflurane was 1.65% +/- 0.53% on loss of consciousness, equaling to that (1.67% +/- 0.26%) at the third-minute ventilation of 3.5% sevoflurane. The blood concentration at the ninth minute was 2.07% +/- 0.26%. CONCLUSION: The depth of sevoflurane after 9 minutes of ventilation of 3.5% sevoflurane is not sufficient to suppress intubation-induced hemodynamic response.

Initial experience with percutaneous edge-to-edge transcatheter mitral valve repair in a tertiary medical center in Taiwan.

BACKGROUND: The transcatheter edge-to-edge mitral valve repair, using MitraClip, has been a safe and effective treatment for severe mitral regurgitation (SMR) in the westerners. However, the therapeutic results of the MitralClip in Taiwan remained elucidated. METHODS: Patients with symptomatic SMR were evaluated by the heart team. For those with high or prohibitive surgical risks, transcatheter mitral valve repair was performed in hybrid operation room. During procedure, continuous hemodynamic monitoring was conducted. Transthoracic echocardiography (TTE), blood tests, and six-minute walk test (6MWT) were performed before and 1-month after surgery. RESULTS: A total of 20 patients (73.4 ± 11.1 years, 85% male) with a mean Euroscore II of 13.2 ± 17.7% and a mean STS score of 8.7 ± 9.0% for mortality were enrolled. After a mean procedural time of 239 ± 95 min, an average of 1.8 ± 0.7 clips were used in each procedure. The procedural successful rate was 95% to achieve mild residual mitral regurgitation. Cardiac output was increased from 3.6 ± 0.9 to 4.6 ± 1.4 (p = 0.008) and V-wave of left atrial pressure declined from 24.4 ± 9.8 to 19.3 ± 7.1 (p = 0.030) immediately during the index procedure. There was no peri-procedural death, myocardial infarction, stroke or any events requiring emergent cardiac surgery. All patients experienced significant improvement in heart failure symptoms. The 6-min walk distance increased from 219.6 ± 118.4 m to 279.1 ± 111.6 (p = 0.04) at 1 month. The echocardiogram further showed significant improvements of mitral regurgitation, pulmonary artery systolic pressure, and the left ventricular end-diastolic volume. CONCLUSION: Trans-catheter edge-to-edge mitral valve repairs are safe and effective in Asians with symptomatic SMR, regarding the improvements of clinical symptoms and exercise capacities. MitraClips is also associated with reverse remodeling of pulmonary hypertension and left ventricular size in patients with SMR.